E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042863 |
E.1.2 | Term | Synovial sarcoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of NY-ESO-1-Specific (c259) T Cells, alone or in combination with other anti-cancer agents, in HLA-A*02:01, HLAA* 02:05 and/or HLA-A*02:06 participants with NY-ESO-1- and/or LAGE-1a positive solid tumors |
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E.2.2 | Secondary objectives of the trial |
- To further evaluate the efficacy of NY-ESO-1 Specific (c259) T Cells alone or in combination with other anti-cancer agents in HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 participants with NY-ESO-1 and/or LAGE-1a positive solid tumors
- To evaluate the safety and tolerability of NYESO- 1 Specific (c259) T Cells alone or in combination with other anti-cancer agents in HLA-A*02:01, HLA-A*02:05 and/or HLAA* 02:06 participants with NY-ESO-1- and/or LAGE-1a positive solid tumors |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
SUBSTUDY 1: GSK3377794 IN PREVIOUSLY UNTREATED ADVANCED METASTATIC OR UNRESECTABLE SYNOVIAL SARCOMA
SUBSTUDY 2: PREVIOUSLY TREATED ADVANCED METASTATIC OR UNRESECTABLE NY-ESO-1-POSITIVE SYNOVIAL SARCOMA |
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E.3 | Principal inclusion criteria |
- Subject must be >=10 years of age at the time of signing the informed consent.
- Subject has a diagnosis of synovial sarcoma confirmed by histology.
- Subject has advanced (metastatic or unrespectable) synovial sarcoma.
- In substudy 1, subject with metastatic synovial sarcoma who is newly diagnosed or previously untreated
- In substudy 2, at the time of treatment, subject has received/completed treatment with anthracycline or anthracycline with ifosfamide for advanced (metastatic or inoperable) disease and progressed.
- Male or female. Contraception requirements will apply at the time of leukapheresis and treatment.
- Subject must be positive for HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles by a validated test in a designated central laboratory. - Subjects tumor has been pathologically reviewed by a designated central laboratory with confirmed positive NY-ESO-1 expression
- Performance status: Eastern Cooperative Oncology Group of 0-1.
- Subject must have adequate organ function and blood cell counts 7 days prior to leukapheresis. - Female subjects of childbearing potential must have a negative urine or serum pregnancy test. -
- Subject has measurable disease according to RECIST v1.1.
- Supportive radiotherapy has not affected >25% of bone marrow.
For a detailed list of Inclusion Criteria's please refer to the protocol |
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E.4 | Principal exclusion criteria |
- In substudy 1, subject has been previously treated for metastatic synovial sarcoma.
Central nervous system metastases.
- Any other prior malignancy that is not in complete remission.
- Previous treatment with genetically engineered NY-ESO-1-specific T cells.
- Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody.
- Prior gene therapy using an integrating vector.
- Previous allogeneic hematopoietic stem cell transplant.
- Clinically significant systemic illness: serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction, that in the judgment of the Investigator would compromise the subject’s ability to tolerate protocol therapy or significantly increase the risk of complications, or, prior or active demyelinating disease.
- Subject has history of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments.
- Uncontrolled intercurrent illness
- Current active liver or biliary disease.
- Pregnant or breastfeeding females (due to risk to fetus or newborn).
- Prior/concomitant therapy: any prior treatment-related toxicities must be Common terminology criteria for adverse events <=Grade 1 at the time of initiating study intervention (except for non-clinically significant toxicities).
- Other standard of care lines of therapy are allowed only if guidelines and washout periods are followed.
- Subject has active infection as defined in the protocol
- Subject has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study.
- Subject had major surgery <=28 days of first dose of study intervention.
For a detailed list of Exclusion Criteria's please refer to the Protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Response Rate (ORR) per RECIST v1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
To further evaluate the efficacy of NY-ESO-1
- Time to Response (TTR)
- Duration of Response (DoR)
- Disease Control Rate (DCR)
- Progression Free Survival (PFS)
- Overall Survival (OS)
To evaluate the safety and tolerability of NYESO-1
- Adverse events (AEs) including serious adverse events (SAEs)
- Incidence, severity and duration of the AEs of special interest (AESI; as defined in protocol)
- Laboratory parameters Replication Competent Lentivirus (RCL)
- T cell Persistence: Maximum transgene expansion (Cmax), time to Cmax (Tmax), and persistence (area under the time curve from zero to time t
AUC(0-t)), as data permit
- Instances of Insertional oncogenesis (IO) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
Germany |
Italy |
Netherlands |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 3 |